P1155: BREXUCABTAGENE AUTOLEUCEL FOR RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA IN ROUTINE PRACTICE: UPDATED REPORT FROM THE US LYMPHOMA CAR T CONSORTIUM
Authors: Y. Wang, P. Jain, F. Locke, M. Maurer, M. Frank, J. Munoz, S. Dahiya, A. Beitinjaneh, M. Jacobs, J. Mcguirk, J. Vose, A. Goy, C. Andreadis, B. Hill, K. Dorritie, O. Oluwole, A. Deol, B. Shah, J. Paludo, T. Wang, R. Banerjee, S. Neelapu, D. Miklos, A. Rapoport, L. Lekakis, A. Ghobadi, Y. Lin, M. Wang, M. Jain
Journal: HemaSphere (2022)

Background: The ZUMA-2 trial and real-world studies showed high efficacy of brexucabtagene autoleucel (brexu-cel) in relapsed/refractory mantle cell lymphoma (MCL). We previously reported an objective response rate (ORR) of 89% in 95 patients receiving standard-of-care brexu-cel in the US Lymphoma CAR T Consortium (Wang et al, ASH 2021). Aims: To update the safety and efficacy results of the Consortium study with more patients and longer follow-up. Methods: Patients who underwent leukapheresis for standard-of-care brexu-cel manufacture at one of the 16 Consortium centers between 8/1/2020 and 12/31/2021 were included. Baseline characteristics, bridging therapy, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and treatment outcome data were collected. Eligibility for ZUMA-2 was retrospectively determined based on characteristics at leukapheresis. Time-to-event data were analyzed using the Kaplan-Meier method. Results: At the data cut-off date of 1/31/2022, 189 patients underwent leukapheresis; 167 (88%) completed infusion and 22 (12%) did not (manufacture failure n=7, death n=6, disease progression n=5, organ dysfunction n=2, complete response [CR] to bridging therapy n=1, patient decline n=1). The median age of the 167 infused patients was 67 years (range 34-89) and 76% were male. 16% had high risk simplified MIPI, 57% had Ki-67 ≥50%, 41% had blastoid or pleomorphic variant, 49% had TP53 alteration, 31% had complex karyotype, 14% had bulky disease (≥10 cm), and 10% had CNS involvement. The median prior lines of therapy was 3 (range 1-10), and 86% were BTKi-exposed (89% of which were refractory). 130 (78%) patients would not have met ZUMA-2 eligibility criteria, and the most common reasons were prior therapies (eg, anthracycline- or bendamustine-naïve [16%], BTKi-naïve [14%], >5 lines of prior therapy [11%]), renal dysfunction (21%), cardiac comorbidities (14%), cytopenias (11%), ECOG PS ≥2 (11%), and CNS involvement (10%). 113 (68%) patients received bridging therapy, which included immunochemotherapy (n=45), BTKi (n=45), venetoclax (n=24), radiotherapy (n=23), corticosteroid (n=18), and lenalidomide (n=6). The median time from leukapheresis to lymphodepletion chemotherapy was 28 days (range 17-140). The rate of CRS was 90% (8% grade ≥3, 1 grade 5), and the rate of ICANS was 61% (32% grade ≥3, 0 grade 5). Medications used to manage CRS and/or ICANS included tocilizumab (76%), corticosteroid (68%), anakinra (16%), and siltuximab (3%). 20% of patients required ICU admission, with a median stay of 3 days (range 1-12); 18% required vasopressors, 3% required mechanical ventilation, and 3% required dialysis. Among 159 evaluable patients, the day 30 ORR was 89%, with 70% CR and 19% partial response (PR). With continued follow-up, the best ORR was 89%, with 80% CR and 9% PR. The best ORR/CR rate were 89%/77% for high Ki-67% (≥50%), 88%/79% for blastoid or pleomorphic variant, 88%/73% for complex karyotype, 90%/72% for TP53 altered, 81%/75% for CNS involved, 89%/79% for BTKi-exposed, 91%/83% for BTKi-naïve, and 89%/78% for ZUMA-2 ineligible. With a median follow-up of 5.6 months (range 0.2-15.3), the 6-month estimates for duration of response, progression-free survival, and overall survival were 67% (95% CI 57-75), 63% (95% CI 54-71) and 85% (95% CI 77-90), respectively. Summary/Conclusion: This updated analysis demonstrated favorable safety and efficacy results of brexu-cel in R/R MCL that are consistent with the initial report. Despite 78% of patients being ineligible for ZUMA-2, the responses, CRS, ICANS and survival outcomes were comparable to ZUMA-2 data.